Effect of sexed semen on different production and functional traits in German Holsteins.

The aim of this study was to analyze possible effects of semen type (conventional vs. female sexed) and calf sex on fertility and production traits. For this purpose, field data of German Holstein heifers in Lower Saxony were evaluated. Sexed semen was mainly used for first insemination. 87.0% female calves were born from sexed semen, while 52.7% female calves were born from conventional semen. Heifers inseminated with sexed semen were on average 43 to 48 days younger at their first calving than heifers inseminated with conventional semen. Calf sex had an influence on the average calving ease and the dystocia rates. Male calves showed higher calving ease scores and caused a higher risk for dystocia than female calves. The semen type had no influence on these characteristics. Within the same calf sex, sexed semen had only minor effects on most traits, except for stillbirth rates: the stillbirth rate for male calves from female sexed semen was 30.6%, which was 2.86 times the stillbirth rate of male calves from conventional semen, possibly due to trisomies. Sexed semen played only a minor role for production traits in first lactations. The extrapolated 305-day milk yield was 200 kg lower for first calf heifers, which were inseminated with sexed semen compared to heifers inseminated with conventional semen. Fat and protein yield were 6 kg to 8 kg lower after use of sexed semen. Animals with female offspring from sexed semen showed higher survival rates than the other groups.

Degradation Kinetics during Oxygen Electrocatalysis on Perovskite-Based Surfaces in Alkaline Media.

The oxygen evolution reaction (OER) during alkaline water electrolysis is the bottleneck of water splitting. Perovskite materials have been particularly proposed as good and economically reasonable electrocatalysts for the OER, showing promise and advantages with respect to classic metallic electrodes. However, the degradation of perovskites during catalysis limits their service lifetime. Recently, the material BaCo0.98Ti0.02O3-δ:Co3O4 was shown to be electrocatalytically and chemically stable during water electrolysis even under industrially relevant conditions. The lifetime of this perovskite-based system is prolonged by a factor of 10 in comparison to that of Pr0.2Ba0.8CoO3-δ and is comparable to that of industrially applied electrodes. Here we report on the degradation kinetics of several OER catalysts at room temperature, comparatively studied by monitoring the oxygen evolution at microelectrodes. A decrease in the reaction rate within a maximum of 60 s is observed, which is related to chemical and/or structural changes at the oxide surface.

Cistopexia videoassistida em cadela com cistocele após prolapso uterino: relato de caso / Videoassisted cystopexy on a female dog with cystocele after uterine prolapse: a case report

O prolapso de vesícula urinária associado ao prolapso uterino é condição rara em cães e gatos. O tratamento preconizado para essa afecção é o reposicionamento anatômico das estruturas afetadas. No presente relato é descrito o manejo por meio de ovariossalpingo-histerectomia por celiotomia e, após dois dias, cistopexia videoassistida. Essa condição, conforme o conhecimento dos autores, não havia sido previamente descrita. A operação apresentou-se como possibilidade viável de tratamento, sem complicações pós-operatórias.(AU)

The urinary bladder prolapse associated with the uterus is a rare condition on dogs and cats. The recommended treatment is the anatomical repositioning of the affected structures by manual reduction or surgery procedure. The present report describes the management by video-assisted cystopexy two days after conventional ovariohysterectomy. This condition, according to the authors' knowledge, had not been previously described. The operation didn't showed postoperative complications, and presented itself as a viable treatment option.(AU)

An inter-machine comparison of tobacco smoke particle deposition in vitro from six independent smoke exposure systems.

There are several whole smoke exposure systems used to assess the biological and toxicological impact of tobacco smoke in vitro. One such system is the Vitrocell® VC 10 Smoking Robot and exposure module. Using quartz crystal microbalances (QCMs) installed into the module, we were able to assess tobacco smoke particle deposition in real-time. We compared regional deposition across the module positions and doses delivered by six VC 10s in four independent laboratories: two in the UK, one in Germany and one in China. Gauge R&r analysis was applied to the total data package from the six VC 10s. As a percentage of the total, reproducibility (between all six VC 10s) and repeatability (error within an individual VC 10) accounted for 0.3% and 7.4% respectively. Thus Gauge R&r was 7.7%, less than 10% overall and considered statistically fit for purpose. The dose-responses obtained from the six machines across the four different locations demonstrated excellent agreement. There were little to no positional differences across the module at all airflows as determined by ANOVA (except for one machine and at three airflows only). These results support the on-going characterisation of the VC 10 exposure system and suitability for tobacco smoke exposure in vitro.

hMLH1 promoter hypermethylation and MSI status in human endometrial carcinomas with and without metastases.

We investigated the methylation status of mismatch repair gene hMLH1 in 80 primary human endometrial carcinomas (ECs) and in 30 metastatic lesions. It was correlated to the expression of hMLH1 protein, microsatellite instability (MSI) of ECs and to the well-known clinico-pathological variables of cancer. The hMLH1 promoter methylation was detected in 24 out of 64 (37.5 %) primary ECs but only in one out of 18 (5.6 %) metastatic lesions investigated. Promoter hMLH1 hypermethylation was found more often in early stage ECs and was associated with a decrease of hMLH1 protein expression immunohistochemically. An inverse relationship between hMLH1 expression and clinical stage of the disease was found (p = 0.048). Interestingly, there was a significant correlation between MSI and hMLH1 protein expression level (p = 0.042). MSI phenotype was found more often in EC metastases compared to the primary tumors (66.7 % vs 29.3 %; p = 0.039). However, neither hMLH1 promoter hypermethylation nor MSI was independent predictive factors for patient's outcome. Using an in vitro model we showed that hMLH1 methylation is reversible. These data showed that hMLH1 methylation with a consequent protein decrease occurred early during EC tumorigenesis and may cause a MSI phenotype, which occurs relatively late. MSI may be an important mechanism supporting further the tumor progression. These findings may have importance for the specific chemosensitization of the primary tumors/metastases and can improve our understanding of endometrial carcinogenesis in humans.

How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale.

Exposure therapy is known to be an effective treatment for anxiety disorders. Nevertheless, exposure is not used as much as it should be, and instead patients are often given supportive medications such as serotonin reuptake inhibitors (SSRIs) and benzodiazepines, which may even interfere with the extinction learning that is the aim of treatment. Given that randomized controlled trials are now investigating a few doses of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') in combination with psychotherapy for treatment-resistant anxiety disorders, we would like to suggest the following three mechanisms for this potentially important new approach: 1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance and 3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations. Thus, MDMA has a combination of pharmacological effects that, in a therapeutic setting, could provide a balance of activating emotions while feeling safe and in control, as described in case reports of MDMA-augmented psychotherapy. Further clinical and preclinical studies of the therapeutic value of MDMA are indicated.

Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55.

We recently reported that hydrogen peroxide-inducible clone-5 (Hic-5, also named androgen receptor-associated protein 55) can bind to the transforming growth factor-beta (TGF-beta)-signaling regulator Smad3, thereby inhibiting certain Smad3-dependent TGF-beta responses. We now show that Hic-5 can also control TGF-beta responses through an alternative mechanism involving Smad7, a key negative regulator of TGF-beta signaling. Hic-5 binds directly to Smad7. This interaction requires the LIM3 domain of Hic-5, and enhances TGF-beta signaling through causing loss of Smad7 protein but not mRNA. Enforced expression of Hic-5 reverses the ability of Smad7 to suppress TGF-beta-induced phosphorylation of Smads 2 and 3 and activation of the plasminogen activator inhibitor-1 promoter (in NRP-154 and PC3 prostate carcinoma and WPMY-1 prostate myofibroblast cell lines). Lentiviral-mediated small-hairpin RNA silencing of endogenous Hic-5 reduced TGF-beta responses in PC3 and WPMY-1 cells. Further work suggests that the level of Smad7 is modulated by its physical interaction with Hic-5 and targeted to a degradation pathway not likely to be proteasomal. Our findings support that Hic-5 functions as a cell-type-specific activator of TGF-beta signaling through its ability to physically interact with and neutralize Smad7.

Rb/E2F4 and Smad2/3 link survivin to TGF-beta-induced apoptosis and tumor progression.

Survivin is a prosurvival protein overexpressed in many cancers through mechanisms that remain poorly explored, and is implicated in control of tumor progression and resistance to cancer chemotherapeutics. Here, we report a critical role for survivin in the induction of apoptosis by transforming growth factor-beta (TGF-beta). We show that TGF-beta rapidly downregulates survivin expression in prostate epithelial cells, through a unique mechanism of transcriptional suppression involving Smads 2 and 3, Rb/E2F4, and the cell-cycle repressor elements CDE and CHR. This TGF-beta response is triggered through a Smad2/3-dependent hypophosphorylation of Rb and the subsequent association of the Rb/E2F4 repressive complex to CDE/CHR elements in the proximal region of the survivin promoter. Viral-mediated gene delivery experiments, involving overexpressing or silencing survivin, reveal critical roles of survivin in apoptosis induced by TGF-beta alone or in cooperation with cancer therapeutic agents. We propose a novel TGF-beta/Rb/survivin axis with a putative role in the functional switch of TGF-beta from tumor suppressor to tumor promoter.

[Anti-metastatic effects of serine protease inhibitors: animal models for analysis]. / Antimetastatische Effizienz synthetischer Serinproteaseinhibitoren: Tiermodelle zur Analyse.

UNLABELLED: To date, no effective adjuvant drug preventing the aggressive spread of tumour cells in late stages of cancer disease or at the time-point of primary tumour removal is available. Although proteases, including members of the large serine protease family, were shown to be promising targets for an anti-metastatic cancer therapy, synthetic protease inhibitors (SPIs) have so far failed to be introduced into the clinic. In addition to considerations in the design of classical in vivo -tests of SPIs as cancer therapy agents, we here review our findings with a straightforward, highly sensitive and very fast in vivo metastasis model and its implications in the development of efficient anti-metastatic SPIs. The lacZ-tagging of tumour cells of this very aggressive T-cell lymphoma model allowed highly sensitive and reproducible detection of metastases within seven days after tumour cell inoculation by X-gal staining of whole organs, allowing cost-effective and material-saving side-by-side screening of a series of SPIs with different specificities for different serine proteases. By establishment of specificity/antimetastatic efficacy correlations we identified coagulation factor Xa as one important target of anti-metastatic SPIs and could use this information for the subsequent design and optimization of factor Xa-specific lead structures. CONCLUSION: We exemplify the usefulness of high-throughput in vivo analysis to direct optimization of lead structures and how this may allow unexpected insight into the molecular biology of metastasis.

Bilateral atypical nodular posterior scleritis.

PURPOSE: To evaluate ocular features of nodular posterior scleritis simulating choroidal melanoma. METHODS: A 60-year old woman presented with blurred vision in her right eye of two weeks duration. On examination she had a mild right-globe proptosis with an episcleral nodular mass as well as a large elevated nonpigmented choroidal mass involving the nasal quadrant. RESULTS: A and B-scan ultrasonography showed a medium to high-reflective solid choroidal mass. MRI demonstrated a bi-convex mass in the medial aspect of the right globe with signal characteristics compatible with choroidal melanoma. Biopsy of the extraocular lesion demonstrated chronic inflammatory cell infiltrate suggestive of posterior scleritis. She responded to corticosteroid therapy. On evaluation 41 months later she was noted to have a similar choroidal mass in the left eye. CONCLUSIONS: The physician should be aware of the clinical manifestations and diagnostic hall marks of nodular posterior scleritis in order to differentiate this inflammatory process from choroidal melanoma.

Mycobacterium genavense infection in a patient with long-standing chronic lymphocytic leukaemia.

We describe the first case of disseminated infection with Mycobacterium genavense in an HIV-seronegative patient with a chronic haematological disorder. Our patient, an 80-year-old woman, had been under long-term treatment with chlorambucil (partially in combination with prednisone) for B-cell chronic lymphocytic leukaemia (B-CLL). When she developed general fatigue and progressive anaemia, as well as progressive lymphadenopathy and splenomegaly, bone marrow biopsy revealed granulomas with acid-fast bacilli, and cultures of both bone marrow and blood grew M. genavense. The patient's CD4+ cell count was approximately 100 microL(-1). Treatment with clarithromycin, ethambutol and rifabutin resulted in improvement of anaemia and general health as well as in regression of lymphadenopathy and splenomegaly.

MR imaging of the thoracoabdominal junction.

Recent advances in MR imaging techniques and its multiplanar capability allow for improved detection and characterization of benign and malignant processes occurring in the thoracoabdominal region. It is important to the staging process of patients with known malignancy to correctly diagnose incidental masses in this region, including hepatic or adrenal lesions, which initially may be identified by other imaging modalities. MR imaging provides a complimentary role in lesion detection and diagnosis that may ultimately affect therapeutic management and outcome.

Liver and bone window settings for soft-copy interpretation of chest and abdominal CT.

OBJECTIVE: We evaluated whether the use of multiple window and level settings on a soft-copy workstation improves diagnostic accuracy on chest and abdominal CT. We hypothesized that routinely using window and level settings during soft-copy interpretation would beneficially affect the final diagnosis without compromising efficiency. MATERIALS AND METHODS: Two hundred three randomly selected abdominal and chest CT scans were interpreted by three radiologists using a four-monitor soft-copy workstation (images per screen, nine; resolution, 2K). After the initial interpretations, all scans were reevaluated by the same radiologists using additional liver and bone window and level settings. Differences in conspicuity and characterization of abnormalities were graded on a three-point scale. RESULTS: Conspicuity and characterization of abnormalities were improved in 67% of abnormal findings (81/121; p = 0.01). Improvement (a finding that substantially affected the final diagnosis) was present in 18% of abnormal findings (22/121; p = 0.04). On average, the evaluation of images at multiple window and level settings required an additional 40 sec per case. CONCLUSION: The use of multiple window and level settings during soft-copy interpretation resulted in improved lesion detectability and characterization with greater diagnostic efficacy. Using soft-copy workstations, radiologists can evaluate images using multiple settings without compromising efficiency.

Imaging features of posttransplantation lymphoproliferative disorder in pancreas transplant recipients.

OBJECTIVE: The purpose of this study was to describe the imaging features of posttransplant lymphoproliferative disorder (PTLD) in pancreas transplant recipients. CONCLUSION: The prominent image finding of PTLD in pancreas transplant recipients is diffuse allograft enlargement, an appearance that may be indistinguishable from the image findings of acute pancreatitis or transplant rejection. However, failure of response to immunosuppressive therapy, presence of intraallograft or extraallograft focal masses, or organomegaly may suggest the diagnosis of PTLD.

MR imaging of prostate cancer.

MR imaging technology is continually evolving and improving. Endorectal MR imaging provides excellent anatomic detail and is the most accurate imaging modality for staging prostate cancer with the ability to affect therapy and cure in many men. Failure to detect microscopic disease and microscopic capsular invasion remain significant weaknesses. MR spectroscopy has great potential for improving the sensitivity and specificity of MR imaging and expanding its diagnostic and staging usefulness.

Percutaneous abdominal and pelvic interventional procedures using CT fluoroscopy guidance.

OBJECTIVE: The purpose of our study was to assess the use of low-milliamperage CT fluoroscopy guidance for percutaneous abdominopelvic biopsy and therapeutic procedures. MATERIALS AND METHODS: We reviewed the clinical records and relevant imaging studies of 97 patients who underwent 119 percutaneous CT fluoroscopy-guided abdominal or pelvic procedures: fluid collection aspiration or drainage catheter insertion (n = 59), biopsy (n = 49), hepatocellular carcinoma ethanol ablation (n = 6), chemoneurolysis (n = 4), and brachytherapy catheter insertion (n = 1). These procedures were guided using a helical CT scanner providing real-time fluoroscopy reconstruction at six frames per second. A control panel and video monitor beside the gantry allowed direct operator control during all interventional procedures. RESULTS: One hundred twelve (94.1%) procedures were successfully performed using either a stand-off needle holder and continuous real-time CT fluoroscopy guidance or incremental manual insertion and intermittent CT fluoroscopy to confirm position. Image quality using low milliamperage was adequate for needle or drainage tube placement in all but two low-contrast liver lesions. Two hematomas were accessed but yielded no fluid on aspiration; one drainage procedure was abandoned after the patient developed endotoxic shock. Imaging of ethanol distribution during injection facilitated tumor ablation and neurolytic procedures. CT fluoroscopy allowed rapid assessment of needle, guidewire, dilator, and catheter placement, especially in nonaxial planes. Average CT fluoroscopy time for biopsy and therapeutic procedures was 133 sec (range, 35-336 sec) and 186 sec (range, 20-660 sec), respectively. CONCLUSION: CT fluoroscopy is a practical clinical tool that facilitates effective performance of percutaneous abdominal and pelvic interventional procedures.

Helical computerized tomography arteriography for evaluation of live renal donors undergoing laparoscopic nephrectomy.

PURPOSE: Traditionally, live renal donors are evaluated with excretory urography and renal arteriography. Helical computerized tomography (CT) arteriography offers a less invasive alternative for demonstrating necessary anatomical information before laparoscopic allograft harvest. We evaluate the accuracy of helical CT arteriography in depicting renal vascular anatomy with an emphasis on the detection of arterial and venous anomalies. MATERIALS AND METHODS: Imaging studies were done on 175 patients according to a standard CT arteriography protocol with early arterial phase scanning (14 to 20-second delay), and 1 mm. axial and 3-dimensional maximum intensity projection reconstructions. Renal vascular anatomy was mapped with attention to aberrant arterial and venous anatomy. Intraoperative findings were correlated at laparoscopic donor nephrectomy. RESULTS: There was overall agreement between CT arteriography and laparoscopic findings in 163 cases (93%). Supernumerary renal arteries were identified in 40 cases (23%). Sensitivity, specificity and accuracy of CT arteriography for arterial anatomy were 91, 98 and 96%, respectively. Cases with less than 2 mm. accessory arteries or early branching single vessels simulating dual arteries were misdiagnosed. Venous anomalies occurred in 11 patients (6.3%). Sensitivity, specificity and accuracy of CT arteriography for venous anatomy were 65, 100, and 97%, respectively. Misdiagnoses included early venous bifurcations and supernumerary tributary veins, which were poorly opacified. CONCLUSIONS: Helical CT is highly accurate and specific for the demonstration of renal arterial anatomy. Poor opacification resulted in a lower sensitivity for venous anatomy. Overall, helical CT provides essential anatomical information, and is an alternative to standard urography and arteriography.